P.g., a Gram-negative bacterium, is one of the main etiological agents of the chronic inflammatory disease, periodontitis. Disease progression is thought to occur as a result of an inadequate immune response, which although happens locally, can also occur distally as a result of the dissemination of P.g. into the circulation. As IL-10 and TLR2 are pivotal molecules in the immune response that P.g. elicits, we hypothesized that TLR2-mediated IL-10 production, following the initial systemic exposure to P.g., inhibits the IFN-γ T cell response. To address this hypothesis, mice were primed with P.g., and the types of cells producing IL-10 and the capacity of T cells to produce IFN-γ following blocking or neutralization of IL-10 were assessed. Our results showed that upon initial encounter with P.g., splenic T cells and CD11b(+) cells produce IL-10, which when neutralized, resulted in a substantial increase in IFN-γ production by T cells. Furthermore, IL-10 production was dependent on TLR2/1 signaling, partly in response to the major surface protein, FimA of P.g. In addition, P.g. stimulation resulted in the up-regulation of PD-1 and its ligand PD-L1 on CD4 T cells and CD11b(+) cells, respectively. Up-regulation of PD-1 was partially dependent on IL-10 but independent of TLR2 or FimA. These results highlight the role of IL-10 in inhibiting T cell responses to the initial systemic P.g. exposure and suggest multiple inhibitory mechanisms potentially used by P.g. to evade the host's immune response, thus allowing its persistence in the host.